tbuckley/cabot-search huggingface dataset:
A single-arm feasibility trial of memantine to prevent chemotherapy-related cognitive decline in patients with early breast cancer.
Authors: Zev Nakamura, Allison Mary Deal, Eliza Myung Park, Kate Stanton, Yesy Lopez, Laura J. Quillen, Erin O'Hare Kelly, Hillary M Heiling, Kirsten A. Nyrop, Emily Miller Ray, Elizabeth Claire Dees, Katherine Elizabeth Reeder-Hayes, Trevor Augustus Jolly, Lisa A. Carey, Yara Abdou, Oludamilola A. Olajide, Megan Ann McNamara, Tim Ahles, Hyman B. Muss
Journal: Journal of Clinical Oncology (2022)

12109 Background: Up to 75% of patients with breast cancer report cognitive decline following chemotherapy. There is no standard of care prevention or treatment of cognitive problems in these patients. This trial (NCT04033419) examines the feasibility of using memantine to prevent cognitive decline during chemotherapy for breast cancer. Methods: We enrolled patients with stage I-III breast cancer scheduled to receive neo/adjuvant chemotherapy. Participants completed a cognitive battery (4 traditional neuropsychological measures and 3 computerized tests) and surveys of self-reported cognition (PROMIS Cognitive Function Short Form 8a) and other neuropsychiatric symptoms at pre-treatment (baseline) and 4 weeks after the last cycle of chemotherapy (post-assessment). Memantine (10 mg BID) was initiated within 1 week of starting chemotherapy and continued until the post-assessment. Adherence and adverse event (AE) monitoring occurred every 2-3 weeks during chemotherapy infusion visits. We used descriptive statistics to evaluate recruitment, retention, and tolerability, adherence, and acceptability of memantine. To evaluate objective cognition, we standardized individual measures using population-based data and averaged them to calculate composite scores of 1) global cognition; 2) attention, working memory, and executive function; and 3) learning and memory. Improvement or decline was defined as ≥ 0.5 SD change between the two assessments. For self-reported cognition, established cutpoints were used to define clinically meaningful change. Results: Of 154 eligible patients approached, 56 (36%) enrolled. Of 51 who completed the baseline assessment and started memantine, 44 (86%) completed the post-assessment; 2 remain active. Among evaluable participants, 92% reported taking ≥ 90% of scheduled doses. Only 36% self-reported cognitive decline, while no change was reported in 57% and improvement in 7%. Decline in objective cognitive domains was observed in 7 - 14% (see Table). There were 7 ≥ grade 3 AEs 2 were possibly related to memantine (diarrhea and hypokalemia). Only 3 participants expressed worry about memantine and only 2 felt that taking memantine disrupted their lives. Conclusions: Our findings suggest that memantine is a safe and feasible intervention for chemotherapy-related cognitive decline and may ameliorate cognitive loss. Randomized controlled trials are needed to determine its preliminary efficacy. Clinical trial information: NCT04033419. [Table: see text]
Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for patients with stage III-N2M0 non-small cell lung cancer (NSCLC): A population-based study.
Authors: Marah Akhdar, Sebawe Syaj, Osaid Alser, Mohamedraed Elshami, Shadi Hamouri
Journal: Journal of Clinical Oncology (2022)

8503 Background: Stage III-N2 non-small cell lung cancer (NSCLC) is a heterogeneous disease with controversial management options. Induction therapy as part of multimodal treatment is the standard of care for Stage III-N2 NSCLC. We aim to investigate the effect of adding radiotherapy to neoadjuvant chemotherapy on survival outcomes. Methods: All adult NSCLC patients diagnosed between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database using ICD-O-3 histologic type coding. Inclusion criteria involved stage III NSCLC patients with ipsilateral lymph node involvement (N2), of any T stage, and with no known distant metastasis (M0). Our main sub-cohorts were patients who either underwent chemoradiotherapy (CRT) or chemotherapy (CT) in neoadjuvant settings. Our primary outcomes were overall survival (OS) and cancer-specific survival (CSS) in months. Cox proportional hazards model was used to analyze the effect of each treatment modality on OS and CSS in univariate and multivariate fashions. Multivariate analysis was adjusted for age, sex, marital status, T stage, resected lymph node status, tumor histology, primary site, laterality, and surgical procedure. Inverse probability treatment weighting (IPTW) was applied to create weighted samples based on study covariates. Results: Our analysis included 1175 patients; 799 (68.0%) underwent neoadjuvant CRT and 376 (32.0%) underwent neoadjuvant CT. Sample median age was 63 (IQR:56-69) years. T2 stage was the most prevalent (N =561, 47.7%), followed by T4 (N=243, 20.7%), T1 (N=228, 19.4%), and T3 (N=143, 12.2%). The main tumor histology was non-squamous cell carcinoma in 773 (65.8%) patients. The upper lobe was the most common primary tumor site (N =788, 67.1%). Patients underwent lobectomy (N=917, 78.0%), pneumonectomy (N=184, 15.7%), or sub-lobar resection (N=69, 5.9%). Adding radiotherapy to chemotherapy showed a slightly higher median OS than chemotherapy alone in neoadjuvant settings (51 vs. 47 months, respectively), and a higher median CSS (75 vs. 59 months, respectively). However, these differences were not statistically significant for OS or CSS (HR = 1.08, 95% CI: 0.91-1.28 and HR = 1.04, 95% CI: 0.89-1.21, respectively). After adjustment, age, T3-T4 stage, non-squamous histology, lower lobe primary site, positive resected lymph nodes, and pneumonectomy were all significant independent predictors for worse OS and CSS. IPTW analysis showed no remarkable survival advantage for CRT patients (HR = 1.15, 95% CI: 0.95-1.40 and HR= 1.12, 95% CI: 0.90-1.39) for OS and CSS, respectively. Conclusions: Adding radiotherapy to neoadjuvant CT did not result in significant survival benefits. Multiple prognostic factors should be taken into consideration when identifying the optimal choice and sequence of multimodal treatment for stage III-N2M0 NSCLC patients.
Characteristics of patients with <i>EGFR</i>-mutant non-small cell lung cancer (NSCLC) at a diverse metropolitan cancer center.
Authors: Lanyi Nora Chen, Benjamin Schluger, Galina Lagos, Brian S. Henick, Benjamin Herzberg, Matthen Mathew, Catherine A. Shu
Journal: Journal of Clinical Oncology (2022)

e20593 Background: Epidermal growth factor receptor-mutated [ EGFR(+)] NSCLC has historically been associated with young, non-smoking patients, especially those of Asian descent. Our medical center serves a diverse population within New York City and includes patients from neighborhoods that are predominantly Hispanic/Latino. We therefore sought to describe the population of patients with EGFR(+) NSCLC treated at our cancer center. Methods: We used our single institution lung cancer database to identify 2092 patients diagnosed with NSCLC between 2013-2019; of these, 375 had EGFR(+) disease. We collected retrospective data on patient demographics and disease outcomes. The chi-square test and t-tests were performed to compare between subgroups of patients. Results: Between 2013-2019, 17.9% of patients diagnosed with NSCLC at our center had an identified EGFR mutation. Incidence of EGFR mutations was higher in Asian NSCLC patients (46.7%) compared to Black (13.1%), white (16.8%), and Hispanic (16.0%) NSCLC patients. Within the 375 patients diagnosed with EGFR(+) NSCLC, however, the distribution was 62.1% white (233 patients), 13.6% Asian (51 patients), 11.2% Hispanic (42 patients), 8.3% Black (31 patients), and 4.8% unknown/other race (18 patients). Over half (57.7%) of patients with EGFR(+) NSCLC had a history of smoking, and most (68.9%) were female. Median age at diagnosis was 71 years. Frequency of tyrosine kinase inhibitor (TKI)-sensitive mutations (L858R and exon 19 deletion) was 85.7% in Hispanic patients, 91.7% in Asian patients, 76.4% in white patients, and 71.0% in Black patients. Significantly more Hispanic EGFR(+) patients were diagnosed at Stage IV (65.4%) compared to 40.4% of Asian patients, 36.7% of Black patients, and 25.7% of white patients (p &lt; 0.02 for all comparisons). Among patients diagnosed with Stage IV disease, Hispanic patients had worse average survival compared to non-Hispanic patients (19.4 months vs. 27.9 months, p = 0.01). Conclusions: EGFR-mutant NSCLC is thought to be especially common among patients who are younger, Asian, and/or never smokers. Our population of EGFR(+) NSCLC, however, encompasses a racially diverse group of patients, most of whom were older at the time of diagnosis and many of whom had a history of smoking. This population of patients, most of whom harbor a TKI-sensitive mutation, supports the use of routine mutational testing that is agnostic to patient demographics. Our data also suggest that Hispanic patients in particular are diagnosed with more advanced disease and have shorter survival; the reasons for such disparities within the EGFR(+) NSCLC population warrant further study.
Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab in treatment-naive advanced/metastatic (adv/met) non–small cell lung cancer (NSCLC) with PD-L1 ≥ 50% and without actionable genomic alterations.
Authors: Benjamin Philip Levy, Martin Reck, James Chih-Hsin Yang, Federico Cappuzzo, Siddhartha Rawat, Jingdong Xie, Priyanka Basak, Enriqueta Felip
Journal: Journal of Clinical Oncology (2022)

TPS3162 Background: First-line treatment with immunotherapy has significantly improved survival in patients with adv/met NSCLC. Pembrolizumab (pembro) as monotherapy has shown superior efficacy compared with chemotherapy in treatment-naive patients with advanced NSCLC and PD-L1 expression ≥50%, but most patients will ultimately experience progression. Dato-DXd is an antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 monoclonal antibody attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. In the ongoing phase 1 TROPION-PanTumor01 study (NCT03401385; DS1062-A-J101), Dato-DXd 6 mg/kg monotherapy demonstrated an objective response rate (ORR) of 28% and a manageable safety profile in pretreated patients with NSCLC. In addition, preclinical studies showed that DXd ADCs combined with an anti–PD-1 antibody was more effective than monotherapy with either agent alone. The tolerability of Dato-DXd 6 mg/kg in combination with pembrolizumab was confirmed in the phase 1b TROPION-Lung02 trial (NCT04526691; DS1062-A-U102). Here we describe the phase 3 TROPION-Lung08 trial evaluating Dato-DXd combined with pembro in treatment-naive patients with adv/met NSCLC. Methods: TROPION-Lung08 (NCT05215340; DS1062-A-U304) is a global, randomized, open-label, phase 3 trial of Dato-DXd plus pembro vs pembro alone in treatment-naive patients with adv/met non-actionable oncogenic driven NSCLC with PD-L1 ≥50% (as determined by PD-L1 IHC 22C3 pharmDx assay). Approximately 740 patients will be randomized to receive pembro 200 mg plus Dato-DXd 6 mg/kg or pembro 200 mg alone every 21 days until discontinuation or 35 cycles of pembro. Randomization will be stratified by Eastern Cooperative Oncology Group performance status (0 vs 1), histology (squamous vs nonsquamous), geographic region (East Asia vs rest of world), and smoking status (former/current vs never). Patients must have stage IIIB/IIIC NSCLC ineligible for curative treatment or stage IV disease. Patients must not have received prior systemic therapy; if patients received neoadjuvant/adjuvant systemic therapy without immune checkpoint inhibitors, it must have been given ≥6 months before the diagnosis of adv/met disease. The primary endpoints are progression-free survival (assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) and overall survival, with target hazard ratios of 0.65 and 0.75, respectively. Secondary endpoints include ORR, duration of response, time to response, disease control rate, safety, and antidrug antibody prevalence. Pharmacokinetic parameters, biomarkers, and patient-reported outcomes will also be explored. Clinical trial information: NCT05215340.
Exploring country priorities and contextual considerations for implementing national cancer control plans (NCCP) among participants of International Cancer Control Partnership (ICCP) ECHO.
Authors: Darya Aleksandrovna Kizub, Linsey Eldridge, Zuzanna Tittenbrun, Mishka K. Cira, Kalina Duncan, Karin Hohman, Leslie Given, Lewis E. Foxhall, Prajakta Adsul
Journal: Journal of Clinical Oncology (2022)

1581 Background: Promoting NCCP implementation by low- and middle-income countries (LMICs) is key to addressing inequities in cancer outcomes and the global burden of cancer. We explored contextual factors that may influence implementation of NCCP priorities in LMICs. Methods: Seven countries participated in the 2021 International Cancer Control Partnership ECHO (R) geared toward creating a community of practice to inform NCCP implementation. Using qualitative methods, we conducted focus group discussions (FGDs) with country teams who were asked to identify NCCP priorities and provide contextual considerations around implementing these in the 12-months program. FGDs were audio-recorded, transcribed, double-coded, and underwent thematic analysis. Results: Thirty-three participants from 6 Sub-Saharan African countries and 1 country in Asia took part in 7 FGDs, including 14 physicians, 9 non-governmental organizations, 6 Ministry of Health/NCCP and 4 cancer registry representatives. All seven country teams (100%) prioritized cancer early detection, especially for cervical (71%) and breast (57%) cancer, including by educating primary care clinicians (57%) and general population (43%) about cancer signs and symptoms. Related contextual factors included late-stage diagnosis of cancer (43%) and low knowledge about cancer among primary care clinicians and the general population (29% each), respectively. Finding resources for implementation of NCCP priorities was important given lack of funding (57% each). Harmonizing programs and building partnerships for implementation (57%) was prioritized given perceived fragmentation of efforts and benefit of leveraging limited resources (29% each). Improving access to treatment (43%) was a priority given a lack of oncology specialists (29%) and unaffordable treatment (14%). Improving access to palliative care (43%), including by writing guidelines (29%), was prioritized due to late-stage diagnosis and insufficient access to palliative care (14% each). Improving cancer registry data was essential for NCCP program planning (43% each), while cancer research (43%) was key to answering specific questions related to cancer registry data (14%) and program impact (29%). Additional contextual considerations for making progress on these priorities dicussed by country teams included leveraging existing programs (100%) and learning from other countries and ICCP technical experts (57% each). Conclusions: There were similarities in country NCCP priorities and contextual factors affecting implementation. These results allow for future exploration of how LMIC country teams implement NCCPs and examine the value of communities of practice promoted by ICCP and facilitated by ECHO, towards improving cancer outcomes.
Cost-effectiveness of mt-sDNA versus mailed FIT outreach for Medicare Advantage enrollees using the CRC-AIM microsimulation model.
Authors: Jay Bhatt, Jing Voon Chen, Vahab Vahdat, A. Fendrick, David A. Lieberman, Durado Brooks, A. Burak Ozbay, Jordan J. Karlitz
Journal: Journal of Clinical Oncology (2022)

e18827 Background: Despite proven effectiveness in reducing colorectal cancer (CRC) cases, screening for CRC remains underutilized, including those enrolled in Medicare Advantage. A mailed fecal immunochemical test (FIT) outreach program may increase CRC screening adherence. This study examined the cost-effectiveness of stool-based tests (FIT and multi-target stool DNA [mt-sDNA]), with FIT offered via a mailed outreach program, in a Medicare Advantage population. Methods: The validated CRC-AIM microsimulation model was used to simulate the costs and clinical outcomes of 2 million average-risk individuals, free of diagnosed CRC at age 40, who initiated CRC screening at age 65. Annual mailed FIT outreach and triennial mt-sDNA were assessed. Test sensitivity and specificity inputs were based on the 2021 United States Preventative Services Task Force modeling study. FIT outreach program cost ($25.92) and direct costs for screening tests, colonoscopies (COLs), complications, and CRC care were included. The model employed a lifetime horizon, 3% discount rates, and a Medicare Advantage perspective. The primary analysis used published real-world adherence rates for stool-based tests and follow-up COLs (FIT/COL: 29%/53%; mt-sDNA/COL: 69.8%/71.5%). Secondary analyses assumed 100% adherence for stool-based tests and/or follow-up COLs and 20% higher than primary analysis for FIT and the corresponding follow-up COLs. Results: In the primary analysis, mt-sDNA had the greatest life-years gained (LYG), incidence reduction (IR), and mortality reduction (MR) and was cost-effective at a willingness-to-pay threshold of $50,000/QALY compared to mailed FIT outreach (Table). This was true when 100% adherence was assumed for follow-up COL and when FIT had 20% higher adherence than the primary analysis. mt-sDNA had 64-129% greater LYG, 79-150% greater IR, and 68-146% greater MR than mailed FIT outreach. When assuming 100% adherence for both screening test and follow-up COL, mt-sDNA was dominated by mailed FIT outreach. Conclusions: Adherence to CRC screening modality and follow-up COL greatly impacts clinical and cost-effectiveness outcomes. Future analysis should consider evidence-based, health plan-specific data to accurately reflect outcomes that aid in payer decision making.[Table: see text]
A phase 1 dose-escalation study of the ABN401 (c-MET inhibitor) in patients with solid tumors.
Authors: Dae Ho Lee, Aflah Roohullah, Byoung Chul Cho, Charlotte Rose Lemech, Paul L. de Souza, Michael Millward, Jun Young Choi, Kyung Eui Park, Na Young Kim, EuiYoung Kim, Saehyung Lee, YeongMun Kim, YOUNGKEE Shin, Ji-Youn Han
Journal: Journal of Clinical Oncology (2022)

3105 Background: MET is a proto-oncogene encoding a receptor tyrosine kinase c-MET for hepatocyte growth factor (HGF). Dysregulated MET signaling by MET exon14 skipping, MET gene amplification and c-MET overexpression in cancer plays a critical role in the development of primary oncogenesis, acquired drug resistance and metastasis. This is a first-in-human trial, phase 1 dose-escalation study of the highly selective MET kinase inhibitor, ABN401. ABN401was evaluated in subjects with advanced solid tumors in South Korea and Australia. Methods: Patients with advanced solid tumors were enrolled in escalating dose cohorts using an accelerated titration design. ABN401 was orally administered daily with 21-day cycle. The primary objective was to evaluate safety and tolerability to define dose-limiting toxicity (DLT), maximum tolerated dose (MTD) according to CTCAE v5. Secondary objectives included pharmacokinetic, recommended phase II dose (RP2D), and preliminary efficacy assessments. Tumor assessment was determined using Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Results: Out of 28 screened patients, 16 patients with 6 different tumor types were treated with ABN401 at daily dose levels of 50, 100, 200, 400, 800 and 1200 mg, 15 patients were evaluated for DLT and one unevaluable. No DLT was observed in all 6 dose levels and the MTD has not been reached. No drug related grade ≥ 3 AEs were observed: only one drug-related SAE (transient peripheral edema) was reported. For treatment response, 5 patients with stable disease, and 2 with partial response were observed. These two patients with partial response had non-small cell lung cancer (NSCLC) with c-MET overexpression and had been treated with ABN401 for 10 and 18 months, respectively. Conclusions: ABN401 dosed up to 1200 mg QD was well tolerated with an acceptable safety profile and promising preliminary antitumor activity in patients with advanced solid tumors. The extension (pilot expansion) for additional efficacy assessment is under way at 800 mg daily dose with c-MET altered NSCLC patients in South Korea and Australia. In addition, a phase 2 expansion study is to start in the United States and South Korea. Clinical trial information: NCT04052971.
Justifying integration of liquid biopsy into routine molecular diagnostics to complement tissue genomic profiling: Experience at Fox Chase Cancer Center.
Authors: Don A Baldwin, Cheyenne Gigli, Yanrong Su, Sandra Viviana Fernandez
Journal: Journal of Clinical Oncology (2022)

e15029 Background: Plasma-based liquid biopsy has rapidly evolved from a novel research tool toward translation into clinical use for many diseases including cancer. While there are still some gaps regarding standardization and clinical utility, as tissue next-gen sequencing had previously faced and overcome, there is a growing body of evidence supporting integration of liquid biopsy into standard of care as a diagnostic tool for precision oncology. Selected from a larger cohort, several cases are presented here illustrating the use of the PGDx elio plasma resolve assay to profile circulating tumor DNA (ctDNA) from patients whose tumor and matched normal DNA had also been characterized by a next-generation sequencing panel. Methods: The PGDx elio plasma resolve assay and bioinformatics detects single and multi-nucleotide variants in 33 genes, select amplifications and translocations, as well as microsatellite instability by sequencing on the Illumina NextSeq 500/550 platform. DNA from matched tumor and normal FFPE samples were assessed using the 275 gene Molecular Diagnostics Laboratory’s Comprehensive Cancer Panel (CCP), also on the NextSeq platform. Selected cases represent the range of diagnostic utility that might be expected from ctDNA. Results: Across all cases, there were varying levels of concordance between tissue and plasma as well as novel variants in the plasma that were not present in the tissue DNA demonstrating the benefit of incorporating ctDNA profiling to capture critical genomic information. In one rectal adenocarcinoma case, DNA variants from the primary tumor were detected in ctDNA eight months later during evaluation of a recurrent tumor, suggesting that plasma profiling might have provided early biomarker detection of recurrence. An aggressive and recurrent melanoma, however, showed no concordance between ctDNA and tumor DNA variants, indicating that some tumors may not shed sufficient DNA into the bloodstream to make ctDNA clinically relevant. Another case of melanoma had concordant detection of the driver BRAF V600E mutation in tumor and ctDNA, but ctDNA also contained a pathogenic ATM truncation not observed in the tumor sample. Current clinical trials are investigating the combination of PARP- and ATR-inhibiting drugs, which causes excessive DNA damage and cell death in the context of ATM-deficient cancers. Conclusions: These cases show that combined tissue and ctDNA profiling at the time of initial diagnosis can reveal tumor heterogeneity or distinct metastases not observed in a selected tissue sample, and that profiling during and after therapy may provide early detection of recurrence, appearance of resistance mutations, or monitoring of measurable residual disease.